title: The osmotic stress response of split influenza vaccine particles in an acidic environment.
abstract: Oral influenza vaccine provides an efficient means of preventing seasonal and pandemic disease. In this work, the stability of envelope-type split influenza vaccine particles in acidic environments has been investigated. Owing to the fact that hyper-osmotic stress can significantly affect lipid assembly of vaccine, osmotic stress-induced morphological change of split vaccine particles, in conjunction with structural change of antigenic proteins, was investigated by the use of stopped-flow light scattering (SFLS), intrinsic fluorescence, transmission electron microscopy (TEM), and hemagglutination assay. Split vaccine particles were found to exhibit a step-wise morphological change in response to osmotic stress due to double-layered wall structure. The presence of hyper-osmotic stress in acidic medium (0.3 osmolarity, pH 2.0) induced a significant level of membrane perturbation as measured by SFLS and TEM, imposing more damage to antigenic proteins on vaccine envelope than can be caused by pH-induced conformational change at acidic iso-osmotic condition. Further supports were provided by the intrinsic fluorescence and hemagglutinin activity measurements. Thus, hyper-osmotic stress becomes an important factor for determining stability of split vaccine particles in acidic medium. These results are useful in better understanding the destabilizing mechanism of split influenza vaccine particles in gastric environment and in designing oral influenza vaccine formulations.
authors.affiliation: Nanotechnology Accelerator and Department of Chemical and Materials Engineering, National Institute for Nanotechnology, University of Alberta, Edmonton, AB, T6G 2M9, Canada, hyojick@ualberta.ca.
authors.forename: Hyo-Jick
authors.initials: HJ
authors.lastname: Choi
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
authors.forename: Carlo D
authors.initials: CD
authors.lastname: Montemagno
mesh_terms: D000143:Acids / Q000737:chemistry; D004355:Drug Stability; D006386:Hemagglutination Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry* / Q000276:immunology; D008027:Light; D046529:Microscopy, Electron, Transmission; D009997:Osmotic Pressure; D010316:Particle Size; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013499:Surface Properties; D015164:Vaccines, Inactivated / Q000737:chemistry / Q000276:immunology
chemical_list: D000143:Acids; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated